Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women

Abstract

Aims: Clinical profiles of women with recurrent urinary tract infection (RUTI) are correlated with their urinary microbes.

Methods: This IRB-approved, cross-sectional study enrolled adult women with RUTI. Urine samples (catheterized and voided) underwent culture by expanded quantitative urine culture (EQUC) and standard urine culture (SUC) methods. A validated symptom questionnaire, relevant clinical variables, and EQUC were used to identify symptom clusters and detect associations with specific urinary microbes.

Results: Most (36/43) participants were postmenopausal; the average age was 67 years. 51% reported vaginal estrogen use; 51% reported sexual activity. Although single symptoms were not associated with specific urinary microbes, EQUC results were correlated with five distinct clinical profile clusters: Group A: odor, cloudiness, and current vaginal estrogen use (no culture result association). Group B: frequency, low back pain, incomplete emptying, and vaginal estrogen (significantly increased proportion of Lactobacillus-positive cultures). Group C: pain/burning, odor, cloudiness, and urgency (high proportions of UTI-associated microbe-positive cultures). Group D: frequency, urgency, pain/burning, and current vaginal estrogen use (increased number of no growth cultures). Group E: frequency, urgency, pain/burning, odor, overactive bladder, and sexually active (significantly increased proportion of Klebsiella-positive cultures).

Conclusions: Distinct clinical profiles are associated with specific urinary microbes in women with RUTI. Refined assessments of clinical profiles may provide useful insights that could inform diagnostic and therapeutic considerations.

Keywords: enhanced urine culture; recurrent urinary tract infection; symptomatology; urinary microbiome; urinary microbiota.

FIGURE 1.

Principal component analysis of EQUC/Cath results from RUTI patients. Unsupervised clustering of the EQUC/Cath urine specimens demonstrated five culture results responsible for differentiation of participant culture results: no growth, Escherichia-positive, Enterococcus-positive, Klebsiella-positive, and Lactobacillus-positive. Clustering demonstrated clear separation between no growth cultures (n=15, black spheres) and cultures with microbial growth along principal component 1 (PC1). The spheres for all negative cultures are overlaid as they are identical in composition. Clustering segregated Escherichia-positive cultures (yellow spheres) from remaining microbe-positive cultures along principal component 2 (PC 2). Escherichia-positive cultures are relatively closely spaced compared to the remaining positive cultures indicating the increased prevalence of monoculture. Principal component 3 segregated the remaining microbe-positive cultures: Enterococcus (blue spheres), Klebsiella (red spheres), and Lactobacillus (purple spheres). The relatively large spread of the spheres from these culture types indicates diversity in the microbial populations.

FIGURE 2.

Heat map of participant symptoms and clinical features for RUTI cohort annotated with presence of major culture type microbe. Heat map demonstrating 5 major clinical profile clusters (black boxes). Group A: participants with odor, cloudiness, and current vaginal estrogen use. This group was not associated with specific culture results. Group B: participants with frequency, low back pain, incomplete emptying, and vaginal estrogen use with significantly increased proportion of Lactobacillus-positive cultures (purple bars) (p=0.047). Group C: participants with pain/burning, odor, cloudiness, and urgency without specific microbe association but high proportion of UTI-associated microbe-positive cultures (blue (Enterococcus) and yellow (Escherichia) bars). Group D: participants with frequency, urgency, pain/burning, and current vaginal estrogen use, with increased number of no growth cultures (black bars). Group E: participants with frequency, urgency, pain/burning, odor, overactive bladder, and sexually active with significantly increased proportion of Klebsiella-positive cultures (red bars) (p=0.025). Colors represent presence (dark blue) or absence (pale blue) of a symptom (listed on the lower aspect of the map) for each subject (listed individually on right side of heat map). p-values based on Chi square test; significant at p < 0.05. Participants with cultures without major culture type microbe are unannotated.